Skip to main content
SpringerLink
Log in

Gut Microbiota and Immune Responses

  • Chapter
  • First Online:
Gut Microbiota and Pathogenesis of Organ Injury

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1238))

Abstract

The gut microbiota consists of a dynamic multispecies community living within a particular niche in a mutual synergy with the host organism. Recent findings have revealed roles for the gut microbiota in the modulation of host immunity and the development and progression of immune-mediated diseases. Besides, growing evidence supports the concept that some metabolites mainly originated from gut microbiota are linked to the immune regulation implicated in systemic inflammatory and autoimmune disorders. In this chapter, we describe the recent advances in our understanding of how host–microbiota interactions shape the immune system, how they affect the pathogenesis of immune-associated diseases and the impact of these mechanisms in the efficacy of disease therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Neish AS (2009) Microbes in gastrointestinal health and disease. Gastroenterology 136:65–80

    Article  PubMed  Google Scholar 

  2. Schaeffer EM (2018) Re: selective depletion of uropathogenic E. coli from the gut by a FimH Antagonist. J Urol 199:874–875

    Google Scholar 

  3. Atala A (2018) Re: selective depletion of uropathogenic E. coli from the gut by a FimH Antagonist. J Urol 199:30–31

    Google Scholar 

  4. Spaulding CN, Klein RD, Ruer S, Kau AL, Schreiber HL, Cusumano ZT, Dodson KW, Pinkner JS, Fremont DH, Janetka JW, Remaut H, Gordon JI, Hultgren SJ (2017) Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist. Nature 546:528–532

    Google Scholar 

  5. Macpherson AJ, Harris NL (2004) Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4:478–485

    Article  CAS  PubMed  Google Scholar 

  6. Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9:313–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, Mulder I, Lan A, Bridonneau C, Rochet V, Pisi A, De Paepe M, Brandi G, Eberl G, Snel J, Kelly D, Cerf-Bensussan N (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31:677–689

    Article  CAS  PubMed  Google Scholar 

  8. Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Berard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Dore J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342:971–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:107–118

    Article  CAS  PubMed  Google Scholar 

  10. Round JL, Mazmanian SK (2010) Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A 107:12204–12209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Faith JJ, Ahern PP, Ridaura VK, Cheng J, Gordon JI (2014) Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Transl Med 6:220ra11

    Google Scholar 

  12. Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Boneca IG, Eberl G (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456:507–510

    Article  CAS  PubMed  Google Scholar 

  13. Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL (2004) Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 172:1118–1124

    Article  CAS  PubMed  Google Scholar 

  14. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341

    Google Scholar 

  15. Kawamoto S, Maruya M, Kato LM, Suda W, Atarashi K, Doi Y, Tsutsui Y, Qin H, Honda K, Okada T, Hattori M, Fagarasan S (2014) Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41:152–165

    Article  CAS  PubMed  Google Scholar 

  16. O’Mahony C, Scully P, O’Mahony D, Murphy S, O’Brien F, Lyons A, Sherlock G, MacSharry J, Kiely B, Shanahan F, O’Mahony L (2008) Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog 4:e1000112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Mazmanian SK, Round JL, Kasper DL (2008) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Nature 453:620–625

    Article  CAS  PubMed  Google Scholar 

  18. Wang Q, McLoughlin RM, Cobb BA, Charrel-Dennis M, Zaleski KJ, Golenbock D, Tzianabos AO, Kasper DL (2006) A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2. J Exp Med 203:2853–2863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Levy M, Thaiss CA, Elinav E (2016) Metabolites: messengers between the microbiota and the immune system. Genes Dev 30:1589–1597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shapiro H, Thaiss CA, Levy M, Elinav E (2014) The cross talk between microbiota and the immune system: metabolites take center stage. Curr Opin Immunol 30:54–62

    Article  CAS  PubMed  Google Scholar 

  21. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, Rudensky AY (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:451–455

    Google Scholar 

  22. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–450

    Article  CAS  PubMed  Google Scholar 

  23. Atarashi K, Tanoue T, Honda K (2010) Induction of lamina propria Th17 cells by intestinal commensal bacteria. Vaccine 28:8036–8038

    Article  CAS  PubMed  Google Scholar 

  24. Liu H, Chen F, Wu W, Cao AT, Xue X, Yao S, Evans-Marin HL, Li YQ, Cong Y (2016) TLR5 mediates CD172alpha(+) intestinal lamina propria dendritic cell induction of Th17 cells. Sci Rep 6:22040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498

    Google Scholar 

  26. Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D (2011) Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. P Natl Acad Sci USA 108:11548–11553

    Article  CAS  Google Scholar 

  27. Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32:815–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Natividad JM, Pinto-Sanchez MI, Galipeau HJ, Jury J, Jordana M, Reinisch W, Collins SM, Bercik P, Surette MG, Allen-Vercoe E, Verdu EF (2015) Ecobiotherapy rich in firmicutes decreases susceptibility to colitis in a humanized gnotobiotic mouse model. Inflamm Bowel Dis 21:1883–1893

    Article  PubMed  Google Scholar 

  29. Mao K, Baptista AP, Tamoutounour S, Zhuang L, Bouladoux N, Martins AJ, Huang Y, Gerner MY, Belkaid Y, Germain RN (2018) Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 554:255–259

    Article  CAS  PubMed  Google Scholar 

  30. Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, Sita G, Racchumi G, Ling L, Pamer EG, Iadecola C, Anrather J (2016) Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. Nat Med 22:516–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lenoir M, Del Carmen S, Cortes-Perez NG Lozano-Ojalvo D, Munoz-Provencio D, Chain F, Langella P, de Moreno de LeBlanc A, LeBlanc JG, Bermudez-Humaran LG (2016) Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer. J Gastroenterol 51:862–873

    Google Scholar 

  32. Brucklacher-Waldert V, Carr EJ, Linterman MA, Veldhoen M (2014) Cellular plasticity of CD4+T cells in the intestine. Front Immunol 5:488

    Google Scholar 

  33. Qian LJ, Kang SM, Xie JL, Huang L, Wen Q, Fan YY, Lu LJ, Jiang L (2017) Early-life gut microbial colonization shapes Th1/Th2 balance in asthma model in BALB/c mice. BMC Microbiol 17:1–8

    Article  CAS  Google Scholar 

  34. Wu W, Liu HP, Chen FD, Liu H, Cao AT, Yao SX, Sun MM, Evans-Marin HL, Zhao Y, Zhao Q, Duck LW, Elson CO, Liu ZJ, Cong YZ (2016) Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-beta production. Eur J Immunol 46:1162–1167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wesemann DR, Portuguese AJ, Meyers RM, Gallagher MP, Cluff-Jones K, Magee JM, Panchakshari RA, Rodig SJ, Kepler TB, Alt FW (2013) Microbial colonization influences early B-lineage development in the gut lamina propria. Nature 501:112–115

    Google Scholar 

  36. Kim CH (2016) B cell-helping functions of gut microbial metabolites. Microb Cell 3:529–531

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Lundell AC, Bjornsson V, Ljung A, Ceder M, Johansen S, Lindhagen G, Tornhage CJ, Adlerberth I, Wold AE, Rudin A (2012) Infant B cell memory differentiation and early gut bacterial colonization. J Immunol 188:4315–4322

    Article  CAS  PubMed  Google Scholar 

  38. Joeris T, Muller-Luda K, Agace WW, Mowat AM (2017) Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol 10:845–864

    Article  CAS  PubMed  Google Scholar 

  39. Bain CC, Bravo-Blas A, Scott CL, Perdiguero EG, Geissmann F, Henri S, Malissen B, Osborne LC, Artis D, Mowat AM (2014) Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 15:929–937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Niess JH, Adler G (2010) Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions. J Immunol 184:2026–2037

    Article  CAS  PubMed  Google Scholar 

  41. Kim M, Galan C, Hill AA, Wu WJ, Fehlner-Peach H, Song HW, Schady D, Bettini ML, Simpson KW, Longman RS, Littman DR, Diehl GE (2018) Critical role for the microbiota in CX(3)CR1(+) intestinal mononuclear phagocyte regulation of intestinal T cell responses. Immunity 49:151–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Muller PA, Koscso B, Rajani GM, Stevanovic K, Berres ML, Hashimoto D, Mortha A, Leboeuf M, Li XM, Mucida D, Stanley ER, Dahan S, Margolis KG, Gershon MD, Merad M, Bogunovic M (2014) Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158:300–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shaw MH, Kamada N, Kim YG, Nunez G (2012) Microbiota-induced IL-1 beta, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine. J Exp Med 209:251–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Foligne B, Nutten S, Grangette C, Dennin V, Goudercourt D, Poiret S, Dewulf J, Brassart D, Mercenier A, Pot B (2007) Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World J Gastroentero 13:236–243

    Article  Google Scholar 

  45. Neil JA, Cadwell K (2018) The intestinal virome and immunity. J Immunol 201:1615–1624

    Article  CAS  PubMed  Google Scholar 

  46. Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LMM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker HC, Kupfer SS, Guandalini S, Semrad CE, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS, Jabri B (2017) Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 356:44–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, Lankowski A, Baldridge MT, Wilen CB, Flagg M, Norman JM, Keller BC, Luevano JM, Wang D, Boum Y, Martin JN, Hunt PW, Bangsberg DR, Siedner MJ, Kwon DS, Virgin HW (2016) Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe 19:311–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Di Sabatino A, Pickard KM, Gordon JN, Salvati V, Mazzarella G, Beattie RM, Vossenkaemper A, Rovedatti L, Leakey NAB, Croft NM, Troncone R, Corazza GR, Stagg AJ, Monteleone G, MacDonald TT (2007) Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. Gastroenterology 133:1175–1187

    Article  PubMed  CAS  Google Scholar 

  49. Brenchley JM, Douek DC (2008) HIV infection and the gastrointestinal immune system. Mucosal Immunol 1:23–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wilen CB, Lee S, Hsieh LL, Orchard RC, Desai C, Hykes BL Jr, McAllaster MR, Balce DR, Feehley T, Brestoff JR, Hickey CA, Yokoyama CC, Wang YT, MacDuff DA, Kreamalmayer D, Howitt MR, Neil JA, Cadwell K, Allen PM, Handley SA, van Lookeren Campagne M, Baldridge MT, Virgin HW (2018) Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 360:204–208

    Google Scholar 

  51. Limon JJ, Skalski JH, Underhill DM (2017) Commensal fungi in health and disease. Cell Host Microbe 22:156–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Leonardi I, Li X, Semon A, Li D, Doron I, Putzel G, Bar A, Prieto D, Rescigno M, McGovern DPB, Pla J, Iliev ID (2018) CX3CR1(+) mononuclear phagocytes control immunity to intestinal fungi. Science 359:232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li XV, Leonardi I, Iliev ID (2019) Gut mycobiota in immunity and inflammatory disease. Immunity 50:1365–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bacher P, Hohnstein T, Beerbaum E, Rocker M, Blango MG, Kaufmann S, Rohmel J, Eschenhagen P, Grehn C, Seidel K, Rickerts V, Lozza L, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Ziegler M, Wisplinghoff H, Heine G, Worm M, Siegmund B, Maul J, Creutz P, Tabeling C, Ruwwe-Glosenkamp C, Sander LE, Knosalla C, Brunke S, Hube B, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A (2019) Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176:1340–1355

    Article  CAS  PubMed  Google Scholar 

  55. Doron I, Leonardi I, Iliev ID (2019) Profound mycobiome differences between segregated mouse colonies do not influence Th17 responses to a newly introduced gut fungal commensal. Fungal Genet Biol 127:45–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T, Ishikawa E, Shima T, Hara T, Kado S, Jinnohara T, Ohno H, Kondo T, Toyooka K, Watanabe E, Yokoyama S, Tokoro S, Mori H, Noguchi Y, Morita H, Ivanov II, Sugiyama T, Nunez G, Camp JG, Hattori M, Umesaki Y, Honda K (2015) Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:367–380

    Google Scholar 

  57. Becattini S, Latorre D, Mele F, Foglierini M, De Gregorio C, Cassotta A, Fernandez B, Kelderman S, Schumacher TN, Corti D, Lanzavecchia A, Sallusto F (2015) T cell immunity. Functional heterogeneity of human memory CD4(+) T cell clones primed by pathogens or vaccines. Science 347:400–406

    Google Scholar 

  58. Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, Rotter JI, Wang HL, McGovern DP, Brown GD, Underhill DM (2012) Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336:1314–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bacher P, Hohnstein T, Beerbaum E, Rocker M, Blango MG, Kaufmann S, Rohmel J, Eschenhagen P, Grehn C, Seidel K, Rickerts V, Lozza L, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Ziegler M, Wisplinghoff H, Heine G, Worm M, Siegmund B, Maul J, Creutz P, Tabeling C, Ruwwe-Glosenkamp C, Sander LE, Knosalla C, Brunke S, Hube B, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A (2019) Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176:1340–1355

    Google Scholar 

  60. Berger AK, Mainou BA (2018) Interactions between enteric bacteria and eukaryotic viruses impact the outcome of infection. Viruses 10:e19

    Google Scholar 

  61. Stecher B, Macpherson AJ, Hapfelmeier S, Kremer M, Stallmach T, Hardt WD (2005) Comparison of Salmonella enterica serovar Typhimurium colitis in germfree mice and mice pretreated with streptomycin. Infect Immun 73:3228–3241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wun K, Theriault BR, Pierre JF, Chen EB, Leone VA, Harris KG, Xiong L, Jiang Q, Spedale M, Eskandari OM, Chang EB, Ho KJ (2018) Microbiota control acute arterial inflammation and neointimal hyperplasia development after arterial injury. PLoS ONE 13:e0208426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hapfelmeier S, Lawson MA, Slack E, Kirundi JK, Stoel M, Heikenwalder M, Cahenzli J, Velykoredko Y, Balmer ML, Endt K, Geuking MB, Curtiss R 3rd, McCoy KD, Macpherson AJ (2010) Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328:1705–1709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Ter Horst R, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ (2016) Linking the human gut microbiome to inflammatory cytokine production capacity. Cell 167:1125–1136

    Google Scholar 

  65. Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, Shaw MH, Kim YG, Nunez G (2012) NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol 13:449–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottiere HM, Dore J, Marteau P, Seksik P, Langella P (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105:16731–16736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 174:3237–3246

    Article  PubMed  Google Scholar 

  68. Brandsma E, Kloosterhuis NJ, Koster M, Dekker DC, Gijbels MJJ, van der Velden S, Rios-Morales M, van Faassen MJR, Loreti MG, de Bruin A, Fu J, Kuipers F, Bakker BM, Westerterp M, de Winther MPJ, Hofker MH, van de Sluis B, Koonen DPY (2019) A proinflammatory gut microbiota increases systemic inflammation and accelerates atherosclerosis. Circ Res 124:94–100

    Article  CAS  PubMed  Google Scholar 

  69. Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A (2011) Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A 108:5354–5359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF (2019) Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation 16:53

    Article  PubMed  PubMed Central  Google Scholar 

  71. Haase S, Haghikia A, Wilck N, Muller DN, Linker RA (2018) Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology 154:230–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mahler A, Balogh A, Marko L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Fratzer C, Krannich A, Gollasch M, Grohme DA, Corte-Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Muller DN (2017) Salt-responsive gut commensal modulates TH17 axis and disease. Nature 551:585–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Usami M, Kishimoto K, Ohata A, Miyoshi M, Aoyama M, Fueda Y, Kotani J (2008) Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells. Nutr Res 28:321–328

    Article  CAS  PubMed  Google Scholar 

  74. Vinolo MA, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R (2011) Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem 22:849–855

    Article  CAS  PubMed  Google Scholar 

  75. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Haghikia A, Jorg S, Duscha A, Berg J, Manzel A, Waschbisch A, Hammer A, Lee DH, May C, Wilck N, Balogh A, Ostermann AI, Schebb NH, Akkad DA, Grohme DA, Kleinewietfeld M, Kempa S, Thone J, Demir S, Muller DN, Gold R, Linker RA (2016) Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 44:951–953

    Article  PubMed  Google Scholar 

  77. Grizotte-Lake M, Zhong G, Duncan K, Kirkwood J, Iyer N, Smolenski I, Isoherranen N, Vaishnava S (2018) Commensals suppress intestinal epithelial cell retinoic acid synthesis to regulate interleukin-22 activity and prevent microbial dysbiosis. Immunity 49:1103–1115

    Google Scholar 

  78. Klebanoff CA, Spencer SP, Torabi-Parizi P, Grainger JR, Roychoudhuri R, Ji Y, Sukumar M, Muranski P, Scott CD, Hall JA, Ferreyra GA, Leonardi AJ, Borman ZA, Wang J, Palmer DC, Wilhelm C, Cai R, Sun J, Napoli JL, Danner RL, Gattinoni L, Belkaid Y, Restifo NP (2013) Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J Exp Med 210:1961–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kaisar MMM, Pelgrom LR, van der Ham AJ, Yazdanbakhsh M, Everts B (2017) Butyrate conditions human dendritic cells to prime type 1 regulatory T cells via both histone deacetylase inhibition and G protein-coupled receptor 109A signaling. Front Immunol 8:1429

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Hsu P, Santner-Nanan B, Hu M, Skarratt K, Lee CH, Stormon M, Wong M, Fuller SJ, Nanan R (2015) IL-10 potentiates differentiation of human induced regulatory T cells via STAT3 and Foxo1. J Immunol 195:3665–3674

    Article  CAS  PubMed  Google Scholar 

  81. Dehner C, Fine R, Kriegel MA (2019) The microbiome in systemic autoimmune disease: mechanistic insights from recent studies. Curr Opin Rheumatol 31:201–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sartor RB (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134:577–594

    Article  CAS  PubMed  Google Scholar 

  83. Tamboli CP, Desreumaux P et al (2004) Dysbiosis as a prerequisite for IBD. Gut 53:1057

    Google Scholar 

  84. Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, Balish E, Hammer RE (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180:2359–2364

    Article  CAS  PubMed  Google Scholar 

  85. Yang I, Eibach D, Kops F, Brenneke B, Woltemate S, Schulze J, Bleich A, Gruber AD, Muthupalani S, Fox JG, Josenhans C, Suerbaum S (2013) Intestinal microbiota composition of interleukin-10 deficient C57BL/6 J mice and susceptibility to Helicobacter hepaticus-induced colitis. PLoS ONE 8:e70783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, Gonzalez A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ (2014) The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15:382–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN, Gordon JI, Onderdonk AB, Glimcher LH (2010) Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8:292–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ohkusa T, Okayasu I, Ogihara T, Morita K, Ogawa M, Sato N (2003) Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis. Gut 52:79–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55:205–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Dicksved J, Halfvarson J, Rosenquist M, Jarnerot G, Tysk C, Apajalahti J, Engstrand L, Jansson JK (2008) Molecular analysis of the gut microbiota of identical twins with Crohn’s disease. ISME J 2:716–727

    Article  CAS  PubMed  Google Scholar 

  91. Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Dore J (2009) Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15:1183–1189

    Article  CAS  PubMed  Google Scholar 

  92. Ishidoh K, Kominami E (2002) Processing and activation of lysosomal proteinases. Biol Chem 383:1827–1831

    Article  CAS  PubMed  Google Scholar 

  93. Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S, Taniguchi T, Morita H, Hattori M, Honda K (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500:232–236

    Article  CAS  PubMed  Google Scholar 

  94. Mukhopadhya I, Hansen R, Meharg C, Thomson JM, Russell RK, Berry SH, El-Omar EM, Hold GL (2015) The fungal microbiota of de-novo paediatric inflammatory bowel disease. Microbes Infect 17:304–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. D’Aoust J, Battat R, Bessissow T (2017) Management of inflammatory bowel disease with Clostridium difficile infection. World J Gastroenterol 23:4986–5003

    Article  PubMed  PubMed Central  Google Scholar 

  96. Borody TJ, Paramsothy S, Agrawal G (2013) Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep 15:337

    Article  PubMed  PubMed Central  Google Scholar 

  97. Zhang L, Dong D, Jiang C, Li Z, Wang X, Peng Y (2015) Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization. Anaerobe 34:1–7

    Google Scholar 

  98. Gavin PG, Mullaney JA, Loo D, Cao KAL, Gottlieb PA, Hill MM, Zipris D, Hamilton-Williams EE (2018) Intestinal metaproteomics reveals host-microbiota interactions in subjects at risk for type 1 diabetes. Diabetes Care 41:2178–2186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Pellegrini S, Sordi V, Bolla AM, Saita D, Ferrarese R, Canducci F, Clementi M, Invernizzi F, Mariani A, Bonfanti R, Barera G, Testoni PA, Doglioni C, Bosi E, Piemonti L (2017) Duodenal mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and microbiota. J Clin Endocr Metab 102:1468–1477

    Article  PubMed  Google Scholar 

  100. Kostic AD, Gevers D, Siljander H, Vatanen T, Hyotylainen T, Hamalainen AM, Peet A, Tillmann V, Poho P, Mattila I, Lahdesmaki H, Franzosa EA, Vaarala O, de Goffau M, Harmsen H, Ilonen J, Virtanen SM, Clish CB, Oresic M, Huttenhower C, Knip M, Group DS, Xavier RJ (2015) The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17:260–273

    Google Scholar 

  101. King C, Sarvetnick N (2011) The Incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions. PLoS ONE 6:e17049

    Google Scholar 

  102. Alam C, Bittoun E, Bhagwat D, Valkonen S, Saari A, Jaakkola U, Eerola E, Huovinen P, Hanninen A (2011) Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice. Diabetologia 54:1398–1406

    Article  CAS  PubMed  Google Scholar 

  103. Neuman V, Cinek O, Funda DP, Hudcovic T, Golias J, Kramna L, Petruzelkova L, Pruhova S, Sumnik Z (2019) Human gut microbiota transferred to germ-free NOD mice modulate the progression towards type 1 diabetes regardless of the pace of beta cell function loss in the donor. Diabetologia 62:1291–1296

    Google Scholar 

  104. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV (2008) Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455:1109–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L (2014) Long term effect of gut microbiota transfer on diabetes development. J Autoimmun 53:85–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Yu H, Gagliani N, Ishigame H, Huber S, Zhu S, Esplugues E, Herold KC, Wen L, Flavell RA (2017) Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development. P Natl Acad Sci USA 114:10443–10448

    Article  CAS  Google Scholar 

  107. Hanninen A, Toivonen R, Poysti S, Belzer C, Plovier H, Ouwerkerk JP, Emani R, Cani PD, De Vos WM (2018) Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut 67:1445–1453

    Article  PubMed  CAS  Google Scholar 

  108. Lau K, Benitez P, Ardissone A, Wilson TD, Collins EL, Lorca G, Li N, Sankar D, Wasserfall C, Neu J, Atkinson MA, Shatz D, Triplett EW, Larkin J (2011) Inhibition of type 1 diabetes correlated to a lactobacillus johnsonii N6.2-mediated Th17 bias. J Immunol 186:3538–3546

    Google Scholar 

  109. Satoh J, Shintani S, Oya K, Tanaka S, Nobunaga T, Toyota T, Goto Y (1988) Treatment with streptococcal preparation (OK-432) suppresses anti-islet autoimmunity and prevents diabetes in BB rats. Diabetes 37:1188–1194

    Article  CAS  PubMed  Google Scholar 

  110. Dolpady J, Sorini C, Di Pietro C, Cosorich I, Ferrarese R, Saita D, Clementi M, Canducci F, Falcone M (2016) Oral probiotic VSL#3 prevents autoimmune diabetes by modulating microbiota and promoting indoleamine 2,3-dioxygenase-enriched tolerogenic intestinal environment. J Diabetes Res 2016:7569431

    Article  PubMed  CAS  Google Scholar 

  111. Greiner TU, Hyotylainen T, Knip M, Backhed F, Oresic M (2014) The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice. PLoS ONE 9:e110359

    Google Scholar 

  112. Marino E, Richards JL, McLeod KH, Yap YA, Stanley D, Mackay CR (2016) Gut microbial metabolites regulate autoimmune T cell responses and protect against type 1 diabetes. Eur J Immunol 46:538–538

    Google Scholar 

  113. Miani M, Le Naour J, Waeckel-Enee E, Verma SC, Straube M, Emond P, Ryffel B, Van Endert P, Sokol H, Diana J (2018) Gut microbiota-stimulated innate lymphoid cells support beta-defensin 14 expression in pancreatic endocrine cells. Prev Autoimmune Diabetes Cell Metab 28:557–572

    CAS  Google Scholar 

  114. Marino E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, McKenzie C, Kranich J, Oliveira AC, Rossello FJ, Krishnamurthy B, Nefzger CM, Macia L, Thorburn A, Baxter AG, Morahan G, Wong LH, Polo JM, Moore RJ, Lockett TJ, Clarke JM, Topping DL, Harrison LC, Mackay CR (2017) Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol 18:552–562

    Article  CAS  PubMed  Google Scholar 

  115. Dos Santos RS, Marroqui L, Velayos T, Olazagoitia-Garmendia A, Jauregi-Miguel A, Castellanos-Rubio A, Eizirik DL, Castano L, Santin I (2019) DEXI, a candidate gene for type 1 diabetes, modulates rat and human pancreatic beta cell inflammation via regulation of the type I IFN/STAT signalling pathway. Diabetologia 62:459–472

    Article  PubMed  CAS  Google Scholar 

  116. Davison LJ, Wallace MD, Preece C, Hughes K, Todd JA, Davies B, Callaghan CO (2018) Dexi disruption depletes gut microbial metabolites and accelerates autoimmune diabetes. BioRxiv

    Google Scholar 

  117. Zhang H, Liao X, Sparks JB, Luo XM, Schloss PD (2014) Dynamics of gut microbiota in autoimmune lupus. Appl Environ Microbiol 80:7551–7560

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Luo XM, Edwards MR, Mu Q, Yu Y, Vieson MD, Reilly CM, Ahmed SA, Bankole AA (2018) Gut microbiota in human systemic lupus erythematosus and a mouse model of lupus. Appl Environ Microbiol 84:e02288

    Google Scholar 

  119. Margolis DJ, Hoffstad O, Bilker W (2007) Association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus. Br J Dermatol 157:540–546

    Article  CAS  PubMed  Google Scholar 

  120. Hevia A, Milani C, Lopez P, Cuervo A, Arboleya S, Duranti S, Turroni F, Gonzalez S, Suarez A, Gueimonde M, Ventura M, Sanchez B, Margolles A (2014) Intestinal dysbiosis associated with systemic lupus erythematosus. MBio 5:e01548–e01514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. He Z, Shao T, Li H, Xie Z, Wen C (2016) Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus. Gut Pathog 8:64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Greiling TM, Dehner C, Chen XG, Hughes K, Iniguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen XD, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA (2018) Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci Transl Med 10:eaan2306

    Google Scholar 

  123. Comte D, Karampetsou MP, Tsokos GC (2015) T cells as a therapeutic target in SLE. Lupus 24:351–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Lopez P, de Paz B, Rodriguez-Carrio J, Hevia A, Sanchez B, Margolles A, Suarez A (2016) Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 6:24072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Ma Y, Xu X, Li M, Cai J, Wei Q, Niu H (2019) Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus. Mol Med 25

    Google Scholar 

  126. Van Praet JT, Donovan E, Vanassche I, Drennan MB, Windels F, Dendooven A, Allais L, Cuvelier CA, van de Loo F, Norris PS, Kruglov AA, Nedospasov SA, Rabot S, Tito R, Raes J, Gaboriau-Routhiau V, Cerf-Bensussan N, Van de Wiele T, Eberl G, Ware CF, Elewaut D (2015) Commensal microbiota influence systemic autoimmune responses. EMBO J 34:466–474

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Chhabra A, Alard P, Jala V, Haribabu B, Kosiewicz M (2014) A role for hormones, gut microbiota and tolerogenic CD103DC in protection of male (NZBxNZW)F1 (BWF1) mice from lupus. J Immunol 192:198

    Google Scholar 

  128. Croia C, Bursi R, Sutera D, Petrelli F, Alunno A, Puxeddu I (2019) One year in review 2019: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 37:347–357

    Google Scholar 

  129. Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, Takeda K (2016) Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol 68:2646–2661

    Article  CAS  PubMed  Google Scholar 

  130. Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J, Nelson H, Matteson EL, Taneja V (2016) An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med 8:43

    Google Scholar 

  131. Picchianti-Diamanti A, Panebianco C, Salemi S, Sorgi ML, Di Rosa R, Tropea A, Sgrulletti M, Salerno G, Terracciano F, D’Amelio R, Lagana B, Pazienza V (2018) Analysis of gut microbiota in rheumatoid arthritis patients: disease-related Dysbiosis and modifications induced by Etanercept. Int J Mol Sci 19:e2938

    Google Scholar 

  132. So JS, Kwon HK, Lee CG, Yi HJ, Park JA, Lim SY, Hwang KC, Jeon YH, Im SH (2008) Lactobacillus casei suppresses experimental arthritis by down-regulating T helper 1 effector functions. Mol Immunol 45:2690–2699

    Article  CAS  PubMed  Google Scholar 

  133. So JS, Lee CG, Kwon HK, Yi HJ, Chae CS, Park JA, Hwang KC, Im SH (2008) Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis. Mol Immunol 46:172–180

    Article  CAS  PubMed  Google Scholar 

  134. Pineda Mde L, Thompson SF, Summers K, de Leon F, Pope J, Reid G (2011) A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med Sci Monit 17:CR347–CR354

    Google Scholar 

  135. Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, Saxelin M, Vapaatalo H, Moilanen E, Korpela R (2003) Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis–a pilot study. Scand J Rheumatol 32:211–215

    Article  CAS  PubMed  Google Scholar 

  136. Liu X, Zeng B, Zhang J, Li W, Mou F, Wang H, Zou Q, Zhong B, Wu L, Wei H, Fang Y (2016) Role of the gut microbiome in modulating arthritis progression in mice. Sci Rep 6:30594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Sato K, Takahashi N, Kato T, Matsuda Y, Yokoji M, Yamada M, Nakajima T, Kondo N, Endo N, Yamamoto R, Noiri Y, Ohno H, Yamazaki K (2017) Aggravation of collagen-induced arthritis by orally administered porphyromonas gingivalis through modulation of the gut microbiota and gut immune system. Sci Rep 7:6955

    Google Scholar 

  138. Teng F, Klinger CN, Felix KM, Bradley CP, Wu E, Tran NL, Umesaki Y, Wu HJJ (2016) Gut microbiota drive autoimmune arthritis by promoting differentiation and Migration of Peyer’s patch T follicular helper cells. Immunity 44:875–888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Aa L-X, Fei F, Qi Q, Sun R-B, Gu S-H, Di Z-Z, Aa J-Y, Wang G-J, Liu C-X (2020) Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol. Acta Pharmacol Sin 41:73–81

    Google Scholar 

  140. Raja R, Hemaiswarya S, Ganesan V, Carvalho IS (2016) Recent developments in therapeutic applications of Cyanobacteria. Crit Rev Microbiol 42:394–405

    CAS  PubMed  Google Scholar 

  141. Doonan J, Tarafdar A, Pineda MA, Lumb FE, Crowe J, Khan AM, Hoskisson PA, Harnett MM, Harnett W (2019) The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis. Nat Commun 10:1554

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Eason RJ, Bell KS, Marshall FA, Rodgers DT, Pineda MA, Steiger CN, Al-Riyami L, Harnett W, Harnett MM (2016) The helminth product, ES-62 modulates dendritic cell responses by inducing the selective autophagolysosomal degradation of TLR-transducers, as exemplified by PKCdelta. Sci Rep 6:37276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Jorgensen SF, Troseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT, Holm K, Hoivik ML, Rashidi A, Dahl CP, Vesterhus M, Halvorsen B, Mollnes TE, Berge RK, Moum B, Lundin KE, Fevang B, Ueland T, Karlsen TH, Aukrust P, Hov JR (2016) Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol 9:1455–1465

    Article  CAS  PubMed  Google Scholar 

  144. Perreau M, Vigano S, Bellanger F, Pellaton C, Buss G, Comte D, Roger T, Lacabaratz C, Bart PA, Levy Y, Pantaleo G (2014) Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders. J Exp Med 211:2033–2045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Bhaijee F, Subramony C, Tang SJ, Pepper DJ (2011) Human immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses. Patholog Res Int 2011:247923

    PubMed  PubMed Central  Google Scholar 

  146. Zhou Y, Ou Z, Tang X, Zhou Y, Xu H, Wang X, Li K, He J, Du Y, Wang H, Chen Y, Nie Y (2018) Alterations in the gut microbiota of patients with acquired immune deficiency syndrome. J Cell Mol Med 22:2263–2271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, Gianella S, Siewe B, Smith DM, Landay AL, Robertson CE, Frank DN, Wilson CC (2014) An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol 7:983–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Lu W, Feng Y, Jing F, Han Y, Lyu N, Liu F, Li J, Song X, Xie J, Qiu Z, Zhu T, Routy B, Routy JP, Li T, Zhu B (2018) Association between gut microbiota and CD4 recovery in HIV-1 infected patients. Front Microbiol 9:1451

    Article  PubMed  PubMed Central  Google Scholar 

  149. Nowak P, Troseid M, Avershina E, Barqasho B, Neogi U, Holm K, Hov JR, Noyan K, Vesterbacka J, Svard J, Rudi K, Sonnerborg A (2015) Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS 29:2409–2418

    Article  CAS  PubMed  Google Scholar 

  150. Hullar MA, Burnett-Hartman AN, Lampe JW (2014) Gut microbes, diet, and cancer. Cancer Treat Res 159:377–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Wroblewski LE, Peek RM Jr, Wilson KT (2010) Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23:713–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Papastergiou V, Karatapanis S, Georgopoulos SD (2016) Helicobacter pylori and colorectal neoplasia: is there a causal link? World J Gastroenterol 22:649–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Park H, Park JJ, Park YM, Baik SJ, Lee HJ, Jung DH, Kim JH, Youn YH, Park H (2018) The association between Helicobacter pylori infection and the risk of advanced colorectal neoplasia may differ according to age and cigarette smoking. Helicobacter 23:e12477

    Article  PubMed  CAS  Google Scholar 

  154. Butt J, Varga MG, Blot WJ, Teras L, Visvanathan K, Le Marchand L, Haiman C, Chen Y, Bao Y, Sesso HD, Wassertheil-Smoller S, Ho GYF, Tinker LE, Peek RM, Potter JD, Cover TL, Hendrix LH, Huang LC, Hyslop T, Um C, Grodstein F, Song M, Zeleniuch-Jacquotte A, Berndt S, Hildesheim A, Waterboer T, Pawlita M, Epplein M (2019) Serologic response to helicobacter pylori proteins associated with risk of colorectal cancer among diverse populations in the United States. Gastroenterology 156:175–186

    Google Scholar 

  155. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, Baselga J, Liu C, Shivdasani RA, Ogino S, Birren BW, Huttenhower C, Garrett WS, Meyerson M (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI (2017) Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS ONE 12:e0171602

    Google Scholar 

  157. Lee YK, Mehrabian P, Boyajian S, Wu WL, Selicha J, Vonderfecht S, Mazmanian SK (2018) The protective role of bacteroides fragilis in a murine model of colitis-associated colorectal cancer. mSphere 3:e00587

    Google Scholar 

  158. Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Sobhani I, Amiot A, Le Baleur Y, Levy M, Auriault ML, Van Nhieu JT, Delchier JC (2013) Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease? Therap Adv Gastroenterol 6:215–229

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  160. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon YCS, Fasani R, Aguirre AJ, Ng K, Elez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M (2017) Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358:1443–1448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Wu J, Li Q, Fu X (2019) Fusobacterium nucleatum contributes to the carcinogenesis of colorectal cancer by inducing inflammation and suppressing host immunity. Transl Oncol 12:846–851

    Article  PubMed  PubMed Central  Google Scholar 

  162. Chang YC, Ching YH, Chiu CC, Liu JY, Hung SW, Huang WC, Huang YT, Chuang HL (2017) TLR2 and interleukin-10 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice. PLoS ONE 12:e0180025

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Zhu W, Miyata N, Winter MG, Arenales A, Hughes ER, Spiga L, Kim J, Sifuentes-Dominguez L, Starokadomskyy P, Gopal P, Byndloss MX, Santos RL, Burstein E, Winter SE (2019) Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer. J Exp Med 216:2378–2393

    Google Scholar 

  164. Wong SH, Kwong TNY, Wu CY, Yu J (2019) Clinical applications of gut microbiota in cancer biology. Semin Cancer Biol 55:28–36

    Article  CAS  PubMed  Google Scholar 

  165. Ohtani N, Kawada N (2019) Role of the gut-liver axis in liver inflammation, fibrosis, and cancer: a special focus on the gut microbiota relationship. Hepatol Commun 3:456–470

    Article  PubMed  PubMed Central  Google Scholar 

  166. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:97–101

    Article  CAS  PubMed  Google Scholar 

  167. Ma C, Han M, Heinrich B, Fu Q, Zhang Q, Sandhu M, Agdashian D, Terabe M, Berzofsky JA, Fako V, Ritz T, Longerich T, Theriot CM, McCulloch JA, Roy S, Yuan W, Thovarai V, Sen SK, Ruchirawat M, Korangy F, Wang XW, Trinchieri G, Greten TF (2018) Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360:eaan5931

    Google Scholar 

  168. Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, Mishra A, Mohan N, Aykut B, Usyk M, Torres LE, Werba G, Zhang K, Guo K, Li Q, Akkad Q, Lall S, Wadowski B, Gutierrez J, Kochen Rossi JA, Herzog JW, Diskin B, Torres-Hernandez A, Leinwand J, Wang W, Taunk PS, Savadkar S, Janal M, Saxena A, Li X, Cohen D, Sartor RB, Saxena D, Miller G (2018)The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 8:403–416

    Google Scholar 

  169. Porter CM, Shrestha E, Peiffer LB, Sfanos KS (2018) The microbiome in prostate inflammation and prostate cancer. Prostate Cancer Prostatic Dis 21:345–354

    Article  CAS  PubMed  Google Scholar 

  170. Fernandez MF, Reina-Perez I, Astorga JM, Rodriguez-Carrillo A, Plaza-Diaz J, Fontana L (2018) Breast cancer and its relationship with the microbiota. Int J Environ Res Public Health 15:e1747

    Google Scholar 

  171. Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S, Dai RM, Kiu H, Cardone M, Naik S, Patri AK, Wang E, Marincola FM, Frank KM, Belkaid Y, Trinchieri G, Goldszmid RS (2013) Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:967–970

    Google Scholar 

  172. Frankel AE, Deshmukh S, Reddy A, Lightcap J, Hayes M, McClellan S, Singh S, Rabideau B, Glover TG, Roberts B, Koh AY (2019) Cancer immune checkpoint inhibitor therapy and the gut microbiota. Integr Cancer Ther 18:1534735419846379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Konishi H, Fujiya M, Tanaka H, Ueno N, Moriichi K, Sasajima J, Ikuta K, Akutsu H, Tanabe H, Kohgo Y (2016) Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis. Nat Commun 7:12365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Gong J, Chehrazi-Raffle A, Placencio-Hickok V, Guan M, Hendifar A, Salgia R (2019) The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies. Clin Transl Med 8:9

    Article  PubMed  PubMed Central  Google Scholar 

  175. Li Y, Tinoco R, Elmen L, Segota I, Xian Y, Fujita Y, Sahu A, Zarecki R, Marie K, Feng Y, Khateb A, Frederick DT, Ashkenazi SK, Kim H, Perez EG, Day CP, Segura Munoz RS, Schmaltz R, Yooseph S, Tam MA, Zhang T, Avitan-Hersh E, Tzur L, Roizman S, Boyango I, Bar-Sela G, Orian A, Kaufman RJ, Bosenberg M, Goding CR, Baaten B, Levesque MP, Dummer R, Brown K, Merlino G, Ruppin E, Flaherty K, Ramer-Tait A, Long T, Peterson SN, Bradley LM, Ronai ZA (2019) Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5(-/-) mice. Nat Commun 10:1492

    Google Scholar 

  176. Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP, Poirier-Colame V, Roux A, Becharef S, Formenti S, Golden E, Cording S, Eberl G, Schlitzer A, Ginhoux F, Mani S, Yamazaki T, Jacquelot N, Enot DP, Berard M, Nigou J, Opolon P, Eggermont A, Woerther PL, Chachaty E, Chaput N, Robert C, Mateus C, Kroemer G, Raoult D, Boneca IG, Carbonnel F, Chamaillard M, Zitvogel L (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350:1084–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragon L, Jacquelot N, Qu B, Ferrere G, Clemenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359:91–97

    Article  CAS  PubMed  Google Scholar 

  179. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359:104–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China

    Lijun Dong

  2. Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China

    Lijun Dong, Jingwen Xie & Youyi Wang

  3. School of Laboratory Medicine and Biotechnology, Institute of Molecular Immunology, Southern Medical University, Guangzhou, 510515, China

    Youyi Wang & Daming Zuo

  4. Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China

    Daming Zuo

Authors
  1. Lijun Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingwen Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Youyi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daming Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daming Zuo .

Editor information

Editors and Affiliations

  1. Department of Pathophysiology, Southern Medical University, Guangzhou, Guangdong, China

    Peng Chen

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dong, L., Xie, J., Wang, Y., Zuo, D. (2020). Gut Microbiota and Immune Responses. In: Chen, P. (eds) Gut Microbiota and Pathogenesis of Organ Injury. Advances in Experimental Medicine and Biology, vol 1238. Springer, Singapore. https://doi.org/10.1007/978-981-15-2385-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation